A proof-of-concept study to investigate the efficacy of heat-inactivated autovaccines in Mycobacterium caprae experimentally challenged goats

Abstract

This study aimed to assess the efficacy of a heat-inactivated Mycobacterium caprae (HIMC) vaccine in goats experimentally challenged with the same strain of M. caprae. Twenty-one goats were divided into three groups of seven: vaccinated with heat-inactivated Mycobacterium bovis (HIMB), with HIMC and unvaccinated. At 7 weeks post-vaccination all animals were endobronchially challenged with M. caprae. Blood samples were collected for immunological assays and clinical signs were recorded throughout the experiment. All goats were euthanized at 9 weeks post-challenge. Gross pathological examination, analysis of lung pathology using computed tomography, and bacterial load quantification in pulmonary lymph nodes (LN) by qPCR were carried out. Only HIMC vaccinated goats showed a significant reduction of lung lesions volume and mycobacterial DNA load in LN compared to unvaccinated controls. Both vaccinated groups showed also a significant reduction of the other pathological parameters, an improved clinical outcome and a higher proportion of IFN-γ-producing central memory T cells after vaccination. The results indicated that homologous vaccination of goats with HIMC induced enhanced protection against M. caprae challenge by reducing lung pathology and bacterial load compared to the heterologous vaccine (HIMB). Further large-scale trials are necessary to assess the efficacy of autovaccines under field conditions.

Comparison of the pathological outcome and disease progression of two Mycobacterium caprae experimental challenge models in goats: endobronchial inoculation vs. intranasal nebulization

“…The involvement of mesenteric LN was a frequent finding in natural settings in a field study carried out in a goat herd, where the most likely transmission pathway was the shared feeders between infected and susceptible animals (Vidal et al, 2017 ). Spread of TB lesions beyond the upper airways and thoracic cavity also occurred in all EB-challenged animals (i.e., all of them showed lesions in the spleen), most likely due to a lymphohematogenous spreading from the primary complex generated in the lungs and pulmonary LN, similar to that reported in previous studies (Arrieta-Villegas et al, 2018 ; Melgarejo et al, 2022 ). This phenomenon could also have occurred in two IN-challenged animals that showed lesions in the spleen (suggestive of hematogenous dissemination), one of which had the most extensive lung TB lesions in the IN-challenged group, without nasal cavity affectation.…”

“…This was also supported by the fact that the cumulative body weight gains of the IN and EB groups tended to converge at the end of the experiment. Previous studies, carried out by our research group, demonstrated that body weight increase in goat kids, experimentally challenged with M. caprae , inversely correlates with pathological TB outcome (Melgarejo et al, 2022 ).…”

“…With the IN nebulization one can control the infection time point and infection dose conditions but still not ensure the infection site within the respiratory tract, resulting in moderate pulmonary TB lesions in only 4/7 animals, probably because a significant fraction of the inoculum was retained in the nasal cavity, whereas all goats infected by EB inoculation showed pulmonary TB lesions as previously described in all experimental infections of goats with M. caprae or M. bovis by this route (Pérez de Val et al, 2011Val et al, , 2012Val et al, , 2013Arrieta-Villegas et al, 2018Melgarejo et al, 2022;Wedlich et al, 2022). However, the EB model, as does the transthoracic one, can induce advanced caseous-necrotizing lesions even in vaccinated individuals, limiting the capacity to predict the protective effect of vaccinated candidates (Arrieta-Villegas et al, 2020).…”

“…Since vaccination of cattle against TB is currently forbidden in the EU due to its interference with the current diagnostic tools used in eradication programs, the goat represents an excellent translational model to investigate the effect of vaccines against TB, which can be tested under field conditions (Pérez de Val et al, 2012 , 2013 ; Bezos et al, 2017 ; Arrieta-Villegas et al, 2018 ; Roy et al, 2018 ; Melgarejo et al, 2022 ). Additionally, goats are also a suitable animal model for human TB because they resemble more closely than small laboratory animals and possess key anatomical features such as the complex bronchial tree (Mclaughlin et al, 1961 ) and lung parenchyma organized in a net of interlobular septa that tend to encapsulate the lesions (Gil et al, 2010 ), the respiratory tract and lung vascularization (Magno et al, 1990 ), and the respiratory lymphoid tissues (Liebler-Tenorio and Pabst, 2006 ).…”

“…In the different TB studies using the goat model, the infection has typically been carried out through the endobronchial route (Pérez de Val et al, 2011 , 2012 , 2013 ; Arrieta-Villegas et al, 2018 , 2020 ; Melgarejo et al, 2022 ), intratracheal aerosolization (Gonzalez-Juarrero et al, 2013 ), and transthoracic injection (Bezos et al, 2010 , 2015 ), all of them inducing primarily pulmonary TB lesions. In particular, the endobronchial approach allows for an accelerated progression of pulmonary TB, which is positive in terms of reducing the duration of the experiments.…”